DESCRIPTION: This application proposes to address the problem of elevated cytotoxic antibodies that precludes individuals from being successfully crossmatched for transplantation. The main objective of the study is to lower anti-HLA antibody titers in these highly sensitized patients in order to reduce the waiting time for kidney transplantation and the incidence of severe rejection and graft loss. The study is based on the hypothesis that administration of pooled human intravenous gamma globulin (IVIG) will reduce anti-HLA antibody activity and reduce allosensitization after transplantation. The applicants present data from their laboratory and from others that strongly suggest that IVIG contains idiotypic anti-anti-HLA antibodies which have the capacity to inhibit anti-HLA antibody cytotoxicity in vitro and in vivo, and possibly enhance allograft survival. The applicants propose a double-blinded, randomized controlled clinical trial of IVIG vs placebo in 100 highly HLA sensitized adult patients with End-Stage Renal Disease (ESRD) that are awaiting kidney transplantation. Patients awaiting transplantation will receive three treatments of IVIG or placebo prior to transplantation and three treatments post-transplantation. The trial will determine if IVIG is superior to placebo in: (1) lowering anti-HLA antibody titers and other measures of alloreactivity, (2) reducing waiting time to transplantation, and (3) improving transplant survival.